U.S. patent application number 16/312922 was filed with the patent office on 2019-08-22 for transfer arrays for simultaneously transferring multiple aliquots of fluid.
The applicant listed for this patent is KIMANTECH, L.L.C.. Invention is credited to Nils Adey, Robert Parry.
Application Number | 20190255524 16/312922 |
Document ID | / |
Family ID | 60992701 |
Filed Date | 2019-08-22 |
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United States Patent
Application |
20190255524 |
Kind Code |
A1 |
Parry; Robert ; et
al. |
August 22, 2019 |
TRANSFER ARRAYS FOR SIMULTANEOUSLY TRANSFERRING MULTIPLE ALIQUOTS
OF FLUID
Abstract
A method for transferring multiple aliquots of fluid, the method
including: contacting the multi well plate or strip with a transfer
array and simultaneously aspirating fluid from multiple wells of
the multi well plate or strip into corresponding hollows in the
transfer array.
Inventors: |
Parry; Robert; (Salt Lake
City, UT) ; Adey; Nils; (Salt Lake City, UT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KIMANTECH, L.L.C. |
Salt Lake City |
UT |
US |
|
|
Family ID: |
60992701 |
Appl. No.: |
16/312922 |
Filed: |
July 12, 2017 |
PCT Filed: |
July 12, 2017 |
PCT NO: |
PCT/US2017/041741 |
371 Date: |
December 21, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62365513 |
Jul 22, 2016 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 3/50851 20130101;
B01L 3/505 20130101; G01N 35/1065 20130101; B01L 2400/0683
20130101; B01L 3/527 20130101; B01L 3/021 20130101; A61J 1/14
20130101; B01L 3/56 20130101; B01L 2300/044 20130101; B01L 3/5025
20130101; B01L 2400/0481 20130101; B01L 2300/0672 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; G01N 35/10 20060101 G01N035/10; B01L 3/02 20060101
B01L003/02 |
Claims
1. A device, a transfer array for simultaneously transferring
multiple aliquots of fluid, the device comprising: a formed upper
sheet and a formed lower sheet contacting the upper sheet, the
upper sheet and lower sheet forming a plurality of hollows between
the upper formed sheet and the lower formed sheet, wherein: the
plurality of hollow are spaced to align with wells in a well plate
or well strip; each hollow of the plurality of hollows comprises a
hole in the lower formed sheet to allow aspiration of fluid into
the hollow and expulsion of fluid from the hollow; and the portion
of the lower sheet forming each hollow extending away from the
upper sheet.
2. The device of claim 1, wherein the portion in the upper sheet
forming each hollow extends away from the lower sheet.
3. The device of claim 1, wherein the upper sheet comprises a first
material and the lower sheet comprises a second, different
material.
4. The device of claim 1, wherein the portion of the lower sheet
forming each hollow further comprises a penetrating tip.
5. The device of claim 1, wherein the portion of the upper sheet
forming each hollow further comprises an area to facilitate
penetration.
6. The device of claim 1, further comprising mechanical connections
between the upper sheet and lower sheet.
7. The device of claim 6, wherein the mechanical connections
comprise one way features.
8. The device of claim 7, further comprising a third sheet, the
third sheet comprising mechanical connections to attach to the
mechanical connections of the upper sheet.
9. The device of claim 8, wherein the third sheet further comprises
penetrating tips aligned with areas of reduced local thickness in
the upper sheet.
10. The device of claim 1, further comprising a deposited
solvent-soluble chemical component on an interior surface of a
hollow.
11. The device of claim 1, wherein an upper portion of the upper
sheet above a hollow comprises a mechanical attachment feature such
that force applied to the mechanical attachment feature may
facilitate expansion of the associated hollow.
12. The device of claim 1, wherein the upper sheet may be pressed
using a flat plate so as to compress all the hollows
simultaneously.
13. The device of claim 1, wherein the lower sheet is formed so as
to seal wells of a multi well plate.
14. A device for providing preloaded aliquots of liquid, the device
comprising: a plurality of transfer pipettes formed from two sheets
of material, each transfer pipette of the plurality of transfer
pipettes holding an aliquot of liquid and a tray conforming to
lower tips of the transfer pipettes, the tray limiting evaporation
of the liquid in the transfer pipettes.
15. The device of claim 14, wherein each transfer pipette further
comprises a bulb on an upper portion of the transfer pipette,
wherein compressing the bulb expels the liquid from the transfer
pipette.
16. A method for transferring liquid from a first multi well plate,
the method comprising: contacting the first multi well plate with a
first transfer array and simultaneously aspirating fluid from
multiple wells of the first multi well plate into corresponding
hollows in the first transfer array.
17. The method of claim 16, further comprising: contacting a second
multi well plate with the first transfer array; and simultaneously
expelling fluid from multiple hollows of the first transfer array
into corresponding wells of the second multi well plate.
18. The method of claim 17, wherein the aspirated fluid is a
solvent which dissolves a chemical and the expelled fluid is a
solution.
19. The method of claim 16, further comprising storing the first
transfer array on a tray, where the first transfer array contains
aspirated fluid.
20. The method of claim 16, further comprising: penetrating hollows
of a second transfer array with lower tips of the first transfer
array; and simultaneously expelling fluid from multiple hollows of
the first transfer array into hollows of the second transfer
array.
21. The method of claim 19, further comprising mechanically
connecting the first transfer array to the second transfer
array.
22. The method of claim 16, wherein contacting the first multi well
plate with a first transfer array seals wells of the first multi
well plate.
Description
BACKGROUND
[0001] Biochemistry and genetic chemistry make extensive use of
multi well plates and multi well strips. A multi well plate is a
flat device with a number of recessed wells. A multi well strip is
similar except the wells are arranged in a linear fashion.
Generally, the wells on a given plate or strip are uniform in size
and arranged in an orderly pattern to facilitate automated or
semi-automated processes. Common configurations of well plates
include: 6, 12, 24, 48, and 96 well formats. Common configurations
of well strips include 8 and 12 well formats. Large well plates may
include hundreds of wells to facilitate automated and/or high
volume testing.
[0002] Each well in a well plate may serve as a separate test
volume. This allows larger numbers of samples in a small area and
may reduce sample preparation time. The compact size, portability,
and ability to keep the test samples organized make well plates
useful tools in evaluating chemical and biological reactions.
[0003] One challenge with well plates is loading or unloading test
components. Loading and/or unloading volumes of fluid into a large
number wells on a plate can be a tedious and time consuming
operation. Further, the use of a single tip, for example, on a
micropipette or a transfer pipette, may allow cross contamination
between wells. Accordingly, it is desirable to enhance the ability
to load and unload multi well plates.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] The accompanying drawings illustrate various examples of the
principles described herein and are a part of the specification.
The illustrated examples are given merely for illustration, and do
not limit the scope of the claims.
[0005] FIG. 1 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0006] FIG. 2 is a top view of an array according to one example of
the principles described herein.
[0007] FIG. 3 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0008] FIG. 4 is a cross-sectional view of two arrays interacting,
according to one example of the principles described herein.
[0009] FIG. 5 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0010] FIG. 6 is a cross-sectional view of an array and a multi
well plate according to one example of the principles described
herein.
[0011] FIG. 7 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0012] FIG. 8 is a cross-sectional diagram of an array element and
a well of a multi well plate, according to one example of the
principles described herein.
[0013] FIG. 9 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0014] FIG. 10 is a cross-sectional diagram of an array element,
according to one example of the principles described herein.
[0015] FIG. 11 is a flowchart of a method according to one example
of the principles described herein.
[0016] FIG. 12 is a cross-sectional diagram of a transfer array
holding fluid and a storage tray according to one example of the
principles described herein.
[0017] FIG. 13 is a cross-section diagram of an array element
showing a method of filling and mixing solutions using a transfer
array according to one example of the principles described
herein.
[0018] FIG. 14 is a cross-sectional diagram of a transfer array in
a conformal well plate according to one example of the principles
described herein.
[0019] Throughout the drawings, identical reference numbers
designate similar, but not necessarily identical, elements.
DETAILED DESCRIPTION
[0020] Transferring fluids into, from, and between well plates is a
common and time consuming task in genetic, chemical, and biological
sciences. These areas have seen increasing discovery and automation
as new test methods are developed and transferred to commercial or
clinical use. Transfer pipettes are one method of transferring
fluids. Similarly, micropipettes with disposable tips may be used
to transfer fluid. These either use a large number of consumables
and/or risk cross contamination between wells.
[0021] This specification describes, among other examples, a
transfer array for transferring fluids to, from, and/or between
well plates and strips. While the described transfer arrays may be
patterned for standard well plates, the designs can also be
patterned to customized or unusual designs with minimal
difficulty.
[0022] In one example, the transfer array is formed from two sheets
of material. The two sheets include a number of transfer elements
arranged to align with wells in a well plate. The transfer elements
are formed from shaped areas of the upper and lower sheet and
contain a hollow area between the sheets. The upper sheet portion
of the transfer element functions as a bulb which may be compressed
to expel fluid and recoils to generate a vacuum to aspirate fluid.
In this manner, the transfer element is similar to a transfer
pipette. The lower sheet portion of the transfer element includes a
tip with an opening. Fluid moves in and out of the transfer element
through a hole in the tip.
[0023] The phrase well plate as used in the specification and the
associated claims should be understood broadly to cover a structure
including a plurality of recessed wells. A well plate may be a
linear array of wells, such as a well strip. A well plate may
contain a two dimensional array of wells as in a traditional well
plate. A well plate may include multiple wells in staggered or
other irregular patterns.
[0024] As used in the present specification and in the appended
claims, the term "a number of" or similar language is meant to be
understood broadly as any positive number comprising 1 to
infinity.
[0025] In the following description, for purposes of explanation,
numerous specific details are set forth in order to provide a
thorough understanding of the present systems and methods. It will
be apparent, however, to one skilled in the art that the present
apparatus, systems and methods may be practiced without these
specific details. Reference in the specification to "an example" or
similar language is understood that a particular feature,
structure, or characteristic described in connection with that
example is included as described, but may not be included in other
examples.
[0026] The present specification, therefore describes a transfer
array for simultaneously transferring multiple aliquots of fluid
including: a formed upper sheet and a formed lower sheet contacting
the upper sheet, the upper sheet and lower sheet forming a
plurality of hollows between the upper formed sheet and the lower
formed sheet, wherein the plurality of hollow are spaced to align
with wells in a well plate or strips in a well strip; each hollow
of the plurality of hollows comprises a hole in the lower formed
sheet to allow aspiration of fluid into the hollow and expulsion of
fluid from the hollow; and the portion in the upper sheet forming
each hollow extending away from the lower sheet and the portion of
the lower sheet forming each hollow extending away from the upper
sheet.
[0027] The present specification also describes a device for
providing preloaded aliquots of liquid, the device including: a
plurality of transfer pipettes formed from two sheets of material,
each transfer pipette of the plurality of transfer pipettes holding
an aliquot of liquid and a tray conforming to lower tips of the
transfer pipettes, the tray limiting evaporation of the liquid in
the transfer pipettes.
[0028] The present specification also describes a method for
transferring liquid from a first multi well plate or strip, the
method comprising: contacting the first multi well plate or strip
with a first transfer array and simultaneously aspirating fluid
from multiple wells of the first multi well plate or strip into
corresponding hollows in the first transfer array;
[0029] Turning now to the figures, FIG. 1 is a cross-sectional
diagram of two transfer elements (110), according to one example of
the principles described herein. The transfer array (100) is made
of an upper sheet (120) and a lower sheet (130). The upper sheet
(120) and lower sheet (130) are attached to as to seal around the
transfer element (110).
[0030] The transfer array comprises a plurality of hollows formed
between an upper sheet (120) and a lower sheet (130). The hollows
serve as transfer elements (110) that aspirate and expel fluid. The
transfer elements (110) can be activated individually, in groups,
or all at once. For example, an entire transfer array (100) may be
loaded in a single operation. The transfer array (100) can then be
moved to a new multi well plate and the solution from the transfer
array discharged by rows into the multi well plate at preselected
time intervals.
[0031] The transfer element (110) is formed between the upper sheet
(120) and the lower sheet (130). The transfer elements (110) may be
formed in a traditional array with rows and columns. The transfer
elements (110) may be formed in other patters or arrangements. The
transfer elements (110) in a given array (100) may be of uniform
size and shape. The transfer elements (110) in a given array (100)
may include a variety of shapes and sizes. For example, each row of
the transfer array may be designed to take up a different volume of
fluid at a given depression of the upper sheet. These different
volumes can then be applied to a well plate to provide a range of
tests. A second transfer array where the rows each contain a
different quantity of a second fluid can then be injected into the
same wells to create a response array.
[0032] The upper sheet (120) may be formed from a variety of
materials. In some examples, the upper sheet is a thermoplastic,
for example, polyethylene (PE, HDPE, LDPE). The upper sheet may be
a thermoset polymer, for example silicone rubber. The upper sheet
(120) may be a composite, for example, a rubberized framework. In
one example, the upper sheet comprises a silicone rubber with a
durometer of 20A to 70A.
[0033] In one example, the upper sheet (120) is molded. The
advantages of molding parts include relatively low process
variation and low cost of the formed parts. In one example, the
molding is injection molding. In one example, the molding is liquid
injection molding (LIM).
[0034] In one example, the upper sheet (120) is thermoformed.
Thermoforming may use less expensive capital equipment than
molding. Thermoforming molds may be cheaper to make and/or modify
than injection molding molds.
[0035] In one example, the upper sheet (120) is cast. For example,
the upper sheet may be case into a mold formed around a 3D printed
or machined part. Casting allows rapid prototyping in the
development of parts, especially parts that will be formed from
thermosets.
[0036] The upper sheet (120) may include a standardized interface
with the lower sheet (130). For example, all upper sheets (120) may
be designed to attach to all lower sheets (130). In another
example, the interfaces can be designed to allow certain
combinations or a single combination of upper sheets (120) and
lower sheets (130) to avoid errors.
[0037] In one example, the upper sheet (120) includes a molded in
reference number that aligns with a feature on the lower sheet
(130). For example, the upper sheet may have a range of bottoms and
each bottom may have a feature, which is associated with the actual
bottom such that when the top sheet and bottom sheet are assembled,
the feature indicates the combination of top sheet and bottom sheet
for a user. These elements may be mechanical features or printed on
one or both sheets (120, 130)
[0038] The lower sheet (130) may be formed of the same material or
a different material as the upper sheet (120). The lower sheet may
(130) be a more rigid material or a more rigid design. In one
example, the lower sheet includes ridges, spars, sprues, or similar
features to provide additional stiffness to the lower sheet
(130).
[0039] In one example, the lower sheet (130) is relatively rigid
compared with the upper sheet (120). For example, the lower sheet
(130) may be formed of polyurethane (PU), polyether ether ketone
(PEEK), polystyrene (PS), polycarbonate (PC), polyethylene
teraphalate (PET), polyimide (PI), and similar materials. The lower
sheet may be injection molded. The lower sheet (130) may be
thermoformed. The lower sheet may be a thermoplastic such as
polyethylene. The lower sheet (130) may be cast, for example from
epoxy or silicone rubber. Because of the relatively flat form of
the lower sheet (130), forming the lower sheet (130) may avoid the
need for a large number of pins or similar elements to form holes
in the lower sheet (130). The lower sheet (130) may be formed of
non-polymers including metal, ceramic, glass, composites, etc.
[0040] In one example, the holes are formed during forming of the
lower sheet (130). In a second example, the holes are formed in a
secondary operation, for example, a punch. The holes in the lower
sheet (130) may be of uniform size and shape. The holes in the
lower sheet (130) may be of different sizes and/or shapes. The
holes in the lower sheet (130) may include a valve (See below, FIG.
7). In one example, the valve is formed using an incomplete punch,
e.g. a crescent or semicircular punch.
[0041] The lower sheet (130) may include features that facilitate
alignment with the wells of a multi well plate. These same features
may facilitate alignment with the upper sheet of a second transfer
array. The portion of the lower sheet (130) that forms the walls of
the transfer elements may press against the walls of the wells of
the well plate. In one example, this facilitates the sealing of the
well plate. In another example, an airway is provided between the
lower sheet (130) and the side of the well of the well plate to
allow airflow in and out of the well. The airway may be sized to
allow airflow while reducing evaporation by restricting
diffusion.
[0042] The lower sheet (130) and the upper sheet (120) may be
connected in a variety of manners. In one example, the upper sheet
(120) and lower sheet (130) include a one way connection such that
the upper sheet (120) snaps into position on the lower sheet (130)
or vice versa. The snap connection may provide a compressive force
to seal the perimeter of the transfer elements between the upper
sheet (120) and the lower sheet (130).
[0043] In one example, the upper sheet and lower sheet are
thermally welded together. This may be accomplished using a variety
of processes, for example, resistive welding. In an example, the
upper sheet and lower sheet are connected with adhesive and/or
solvent bonding. The surfaces of the upper sheet (120) and lower
sheet (130) that contact each other may be modified to increase
bond strength or bonding reliability. This may include texturing
the mold or providing ridges, groves, primer, weld features, etc.
to strengthen connection between the upper sheet (120) and the
lower sheet (130).
[0044] The portion of the lower sheet (130) that forms the bottom
of the transfer element (110) may include a piercing tip and/or a
separating or parting edge/rib/ridge to allow one transfer array to
interlock with a second transfer array and receive and/or transfer
fluid through the first array.
[0045] The piercing tip may be symmetrical. The piercing tip may be
asymmetrical. The piercing tip may be a formed or sharpened using a
secondary operation to reduce the force to penetrate an upper sheet
(130). The lower sheet (130) may include parting ribs or other
elements to facilitate opening the upper sheet (120). In one
example, the upper sheet is a highly crystalline thin polymer film
such as BOPET. This may provide adequate mechanical strength and
flexibility while still allowing easy penetration by a penetrating
tip and propagation of the opening by a parting rib.
[0046] FIG. 2 is a top view of a transfer array (100), according to
one example of the principles described herein. The transfer array
(100) includes a number of transfer elements (110). The transfer
elements (110) may be organized in standardized rows and columns.
The transfer elements (110) may be arranged to correspond with the
locations of wells in a well plate. The transfer elements may form
a variety of patterns. For example, the transfer array may include
transfer elements over some rows and not over other rows. The
transfer array (100) may have transfer elements for every other
well or every third well of the well plate. The ability to select
patters of transfer elements and patterns of volumes of transferred
fluid in different elements allows the rapid loading of a well
plate with a pattern of test volumes.
[0047] The transfer array may be loaded from a well plate. The
transfer array (100) may be loaded from a common reservoir. In one
example, the common reservoir includes weep holes or an overflow
weir to allow rapid filling of the transfer array from a fixed
immersion depth without having to individually pipette fluid into
wells of a transfer plate. In one example, the plate can be tilted
to cause fluid to flow from an overflow reservoir back into the
transfer area in order to load a second transfer array.
[0048] In one example, the transfer array (100) includes stops on
the upper sheet (120) and/or the lower sheet (130). The stops limit
travel of a plate compressing the upper sheet during loading and
unloading. The stops may facilitate reproducible filling or
discharge of the transfer array. In one example, the pressor plate
includes a hole or window to avoid a first set of stops and travel
to a second set of stops. For example, depending on the plate use,
the transfer elements (110) may be loaded with 500 microliters or 1
milliliter of solution.
[0049] FIG. 3 is a cross-sectional diagram of an array element,
according to one example of the principles described herein. FIG. 3
shows an array element (110) with formed of an upper sheet (120)
and a lower sheet (130). The array element (110) also includes an
access point (140).
[0050] The access point (140) facilitates the use of multiple
transfer arrays (100). The access point (140) is an area in the
upper sheet that is part of the transfer element that is designed
to facilitate injection or aspiration of material into a second
transfer array (100) through a first transfer array (100). In one
example, the access point is an area of reduced but non-zero local
thickness in the upper sheet. The access point (140) may be an area
of different mechanical properties that facilitate penetration of
the upper sheet (130). For example, if the upper sheet is composed
of silicone rubber, the access point may be degraded with UV
radiation or similar so as to be relatively stiff and non-pliable.
The access point (140) may be an insert molded into the upper sheet
(130).
[0051] The access point (140) may be sealed by a second film or
foil that is over molded by the upper sheet (120). In one example,
the access point (140) is covered by a metal foil. In one example,
the access point (140) is covered by a biaxially oriented ethylene
terephthalate (BOPET) film.
[0052] FIG. 4 is a cross-sectional view of two transfer arrays
interacting, according to one example of the principles described
herein. The first transfer array (100) sits on a well plate (450).
The second transfer array (400) has been previously loaded with
fluid. The second transfer array descends and penetrates the first
transfer array. The fluid in the second transfer array may then be
expelled into the wells of the well plate (450). In this manner
fluids can be added sequentially to the reaction wells without
having to unseal it, thereby avoiding exposing the surrounding
environment to the contents of the well. Fluid in the well plate
(450) may also be aspirated into the second transfer array
(400).
[0053] In one example, the tip of the transfer element (110) is
designed to interface with the inside of the tip of a second
transfer element (110). This may help isolate any residual volume
between the first and second transfer arrays. In this example, the
outer diameter of the external portion and the inner diameter of
the tip of the transfer element are selected to interlock. The
outer circumference of the tip may be tapered toward the lower end
of the tip in order to help align the two transfer arrays. In one
example, the external length of the tip is correlated with a height
of stops to support the lower sheet (130) of the second transfer
array (400). The stops may serve the dual function of limiting the
travel of the second transfer array and stabilizing the second
transfer array on the first transfer array.
[0054] FIG. 5 is a cross-sectional diagram of an array element,
according to one example of the principles described herein. FIG. 5
shows a variety of shapes for the upper sheet (120) portions of
transfer elements. These shapes can be mixed and matched on a
single upper sheet (120). In another example, the upper sheet may
include a single shape configuration.
[0055] The upper sheet (120) may be designed to have a non-linear
relationship between volume change and compression. In one example,
the upper sheet (120) may be designed to minimize volume change
with respect to compression at various levels of compression
corresponding to expected transfer volumes. For example, the upper
portion may include a plurality of accordion like elements of
different thicknesses that allow for the targeting multiple
specific transfer volumes.
[0056] FIG. 6 is a cross-sectional view of an array and a multi
well plate according to one example of the principles described
herein. In this view the upper sheet (120) and lower sheet (130) of
the transfer array (100) are visible. The transfer array (100) is
on a well plate (450). A presser plate (660) with a plurality of
pins is shown pressing the upper sheet (120) in order to actuate
the transfer elements (110) and expel the fluid from the transfer
array (100) into the well plate (450). The transfer array (100) may
include a number of stops (665).
[0057] The pressor plate (660) may include a number of pins as
shown. The pins may be of uniform height. The pins may be of
different heights to produce different amounts of fluid transfer.
The use of a pressor plate (660) with pins offers flexibility in
terms of process
[0058] As shown in FIG. 6, the pressor plate (660) may be flat. The
use of a flat pressor plate (660) offers some advantages in
alignment. For example, with pin based plates, small changes in the
pin position on the upper sheet (120) over the transfer element
(110) may change the volume vs. height relationship. The use of a
flat plate avoids this issue. A flat pressor plate (660) is also
less susceptible to incidental damage that pins, especially the
pins near the periphery of the array. Finally, pins will have some
inherent variation in their diameter which, depending on the shape
of the upper sheet (120) portion of the transfer element may
increase the variation in the array.
[0059] The pressor plate (660) may include a plurality of rounded
indents as shown in FIG. 6. The rounded indents may provide a
different compression profile than that of a flat plate. The
rounded indents may provide a larger contact area between the
pressor plate (660) and the upper sheet (130). In some examples,
the rounded indents may provide greater control over fluid
delivery. The rounded indents may be less susceptible to alignment
errors than the pins. The rounded indents may be more susceptible
to alignment errors than the plate pressor plate (660).
Accordingly, there are design tradeoffs that should be considered
when implementing these features depending on the priorities of the
user.
[0060] The pressor plate (660) may interact with a recovery feature
on the upper sheet (120) and/or lower sheet (130). The recovery
feature may be a stern (150) The recovery feature may be eyelets,
pins, hooks, or similar structures that allow interaction with the
pressor plate (660). In one example, each transfer element (110)
has a recovery feature located on the upper sheet (120) of the
transfer element (110). The recovery feature facilitates aspiration
of fluid in the transfer element (110). The recovery feature allows
the use of a wide range of materials for the upper sheet (120) that
would otherwise not have adequate elastic recoil. In one example,
the pressor plate is able to gasp or otherwise pull on the recovery
feature. In one example, the pressor plate includes a plurality of
holes. The holes may be tapered to facilitate alignment. The holes
may receive a stem (150) extending upward from each transfer
element. The stems (150) may be held relative to the pressor plate
(660). In one example, the pressor plate (660) includes a second
plate that slides laterally to the pressor plate (660). The second
plate includes a set of aligned holes that receive the stems (150).
When the second plate slides, the relative motion of the pressor
plate (660) and the second plate locks the stems (150) in
place.
[0061] The pressor plate (660) may include hooks to interact with
eyelets or hooks associated with the transfer element (110). In one
example, the hooks on the pressor plate (660) are barbed pins. The
barbed pins deflect a portion of the upper sheet (130) during
compression. On retraction, the barb on the pin exerts upward force
on the upper sheet (130) to facilitate aspiration of fluid.
[0062] The pressor plate (660) may include stops over portions of
the upper sheet. The stops may be similar to long pins that
eventually touch the upper sheet (120) during dispensing and/or
aspirating and help control the travel of the pressor plate (660).
Stops may be useful for ensuring uniform compression over the
entire transfer array. In one example, stops are used with a plate
on a ball and socket joint. This allows the stops to provide the
functionality of leveling the pressor plate (660). In another
example, the stops can be aligned to create a desired final slope
for the pressor plate in order to provide a gradient of pressure
across a transfer array.
[0063] The upper sheet (120) and/or lower sheet (130) may include
stops (665). The stops (665) may be features of the well plate
(450). The stops (665) may serve as both stops (665) and alignment
features or guides for the upper sheet (120) and/or lower sheet
(130). The stops (665) may be formed of the same material as the
upper sheet (120). The stops (665) may be formed of the same
material as the lower sheet (130). The stops (665) may be formed of
the same material as the well plate (450). The stops (665) may be
formed of a different material, for example, a metal or structural
polymer (e.g. polycarbonate). The stops (665) may limit travel of
the pressor plate (660). The stops (650) may stabilize the position
of the upper sheet (120), lower sheet (130), and well plate (450)
relative to each other. The stops (665) may include reversible
locking features or one way clasping features.
[0064] FIG. 7 is a cross-sectional diagram of a transfer element
(110), according to one example of the principles described herein.
The transfer element (110) includes an upper sheet (120) and lower
sheet (130). The hole in the lower sheet (130) that allows fluid in
and out of the transfer element (110) includes a valve (770). FIG.
7 also shows an example of an alignment pin (780).
[0065] The inclusion of the valve (770) in the tip of the transfer
element (110) may facilitate larger transfer volumes in the
transfer elements (110). The valve (770) may reduce evaporation of
fluid in the transfer element during storage, for example, by
reducing the surface area exposed to the outside environment. While
the valve (770) is shown as a flap valve, other designs are
possible.
[0066] In one example, the valve (770) is formed during molding the
lower sheet (130). The valve (770) may be formed by a secondary
operation, for example a partial punch with a crescent or circular
punch may be used to form the valve.
[0067] The alignment pin (780) may protrude through a hole in the
upper sheet (120). The alignment pin (780) may be an integrated
part of the lower sheet (130). In one example, the alignment pin is
integrated into the well plate (450) and both the upper sheet and
lower sheet (130) include holes or other features to take advantage
of the alignment pin (480).
[0068] The alignment pin (780) may have a conical or rounded top to
help guide upper sheet (120) and/or lower sheet (130) into
position. In one example the alignment pin includes ratchet or
similar clasping device to secure the upper sheet (120) and lower
sheet (130) relative to each other. This may be as simple as an
enlarged section above a reduced section. Such devices may include
tapers to facilitate attachment. The position of the alignment pins
(780) may be used to limit which upper sheets (120) can be attached
to a given lower sheet (130). The position of the alignment pin may
provide information about the type of bottom sheet used. For
example, there may be a plurality of holes in the upper sheet that
can accommodate a variety of patterns of alignment pins. The holes
may have symbols or text near them to indicate the type of lower
sheet associated with pins in that location. The alignment pins may
also perform some of the functions of the stops (660).
[0069] FIG. 8 is a cross-sectional diagram of a transfer element
(110) and a well of a multi well plate (450), according to one
example of the principles described herein. The transfer element
(110) is formed of an upper sheet (120) and a lower sheet (130). In
FIG. 8, the portion on the left shows the before condition. The
well holds an amount of fluid. A transfer element (110) with a
second fluid is brought into contact with the fluid in the well.
The fluid in the well and fluid in the transfer element are mixed
by aspiration. In one example the fluid in the well and fluid in
the transfer element are mixed using multiple aspiration/expulsion
cycles. As seem on the right, the mixed fluid is then aspirated
into the transfer element (110), either to react and/or be
transferred to a different location for further processing.
[0070] FIG. 9 is a cross-sectional diagram of an array element
(110) and a well of a multi well plate (450), according to one
example of the principles described herein. FIG. 9 shows a method
for removing magnetic beads (990) from a sample without exposing
the sample to a potential contaminant source.
[0071] In this example, a solution containing magnetic beads (990)
is aspirated into the transfer element (110). The solution may be
aspirated and expelled multiple times. The magnetic beads (990) are
attracted to a magnet (980) or magnetizable component proximal to
the volume of the transfer element (110). This causes the magnetic
beads (90) to adhere to the side of the transfer element (110).
Once more or all of the magnetic beads have been captured, the
solution in the transfer element (110) can be expelled and the
solution further processed or tested without the interference of
the magnetic beads. Alternatively, the sample of interest may be
captured by the magnetic beads, the fluid expelled from the
transfer element (110), and a new fluid aspirated into the transfer
element (110).
[0072] In one example, the magnets (980) are located on a comb-like
structure that is inserted laterally across the transfer array. The
tines of the comb-like structure have magnets (980) located so as
to proximal to the desired transfer elements (110). In one example,
the tines with the magnets (980) or magnetizable material (e.g.
iron) is curved to contour around the outside of the transfer
elements (110) of the transfer array (100).
[0073] FIG. 10 is a cross-sectional diagram of an array element,
according to one example of the principles described herein. FIG.
10 shows a chemical (1005) located on the inside of the transfer
element (110) part of the lower sheet (130). The reagent could also
be located on the upper sheet (120).
[0074] In one example, the lower sheet (130) has a solid chemical
(1005) applied to the inner surface. The solid chemical (1005) can
be applied as a droplet and allowed to dry. The solid chemical
(1005) may be applied as a film, a paste, a slurry, a vesicle, a
micelle, etc. In one example, the chemical (1005) is applied to the
lower sheet (130) prior to putting the upper sheet (120) and lower
sheet (130) together. The lower sheet (130) may include a contoured
portion to facilitate placement of droplets while drying. For
example, the edges of the lower sheet (130) may include angled
flaps to help stabilize the lower sheet at an angle. The inner
surface of the lower sheet (130) may include flat areas or divots
that facilitate holding droplets of fluid while the lower sheet
(130) is at an angle. In another example, the chemical (1005) may
be applied as a spray or other technique which allows the chemical
(1005) to solidify on the interior surface of the transfer element
(110). The chemical can be any component that might be added to a
well plate. Preferably, the chemical (1005) is stable and does not
degrade between application and use. In some examples, the transfer
array is shipped with the chemical preloaded to facilitate rapid
work. In some examples, the material of the lower sheet (130) may
be selected to contain the chemical (1005) without reacting with
the chemical. While the chemical (1105) may be solid, the chemical
(1105) may also be a viscous fluid, a slurry, a thixotropic fluid,
a suspension, an emulsion, etc. as long as the chemical (1005) can
remain stable on the inner wall of the transfer element (110)
between the time of application and the time of use.
[0075] In one example, the transfer element (110) aspirates a fluid
that dissolves the chemical (1005) to form a solution. In some
examples, the transfer element (110) may aspirate and expel the
fluid multiple times to enhance dissolution by enhancing the local
mixing and sheer. The speed and profile of aspiration and expulsion
of the fluid may be optimized based on the solution, temperature,
solid material, etc. In one example, the chemical (1005) includes a
mixture of high solubility and low solubility materials, the high
solubility material being used to stabilize the low solubility
material as a fine particulate in order to enhance the rate of
dissolution. In another example, the chemical (1005) is a liquid
contained in a soluble film.
[0076] FIG. 11 is a flowchart of a method (1100) for transferring
liquid from a first multi well plate according to one example of
the principles described herein. The method comprises: contacting
(1110) the first multi well plate with a first transfer array and
simultaneously aspirating (1120) fluid from multiple wells of the
first multi well plate into corresponding hollows in the first
transfer array.
[0077] Contacting (1110) the first multi well plate with a first
transfer array may include the use of alignment features on the
multi well plate and/or the transfer array.
[0078] Simultaneously aspirating (1120) fluid from multiple wells
of the first multi well plate into corresponding hollows in the
first transfer array may include moving a pressor plate to allow
recoil of the upper sheet (120). In some examples, the pressor
plate mechanically connects with the upper sheet (120). For
example, the upper sheet (120) may include bars, ribs, hooks,
eyelets, or similar features that mechanically couple the pressor
plate and the upper sheet (120). These features may allow the
pressor plate to also pull the upper sheet (120) away from the
lower sheet (130) to better control aspiration of fluid into the
hollows and/or transfer elements (110).
[0079] The method may also include other elements, for example,
contacting a second multi well plate with the first transfer array;
simultaneously expelling fluid from multiple hollows of the first
transfer array into corresponding wells of the second multi well
plate; attaching the transfer array (100) to the second multi well
plate (450) in order to seal it and/or storing the transfer array
(100) on a tray, where the transfer array (100) contains aspirated
fluid; penetrating hollows of a second transfer array (100) with
lower tips of the first transfer array (100); and/or simultaneously
expelling fluid from multiple hollows of the first transfer array
(100) into hollows of the second transfer array (100). The method
may further comprise mechanically connecting the first transfer
array (100) to the second transfer array (100).
[0080] In one example, the aspirated fluid is a solvent which
dissolves a chemical and the expelled fluid is a solution.
Contacting the first multi well plate (450) with a first transfer
array (100) may seal wells of the first multi well plate (450).
[0081] FIG. 12 is a cross-sectional diagram of a transfer array
holding fluid and a storage tray accordingly to one example of the
principles described herein. The transfer array (100) is shown on a
storage tray (1215). The storage tray helps reduce spills and
leakage during the storage of fluids in the transfer array (100).
The storage tray includes wells similar to a well plate (450). In
some examples, the storage tray also includes a pin to seal or
block the tip of the transfer elements (110) to further reduce
evaporation and provide stability during transportation or
shipping.
[0082] The pin may be tapered or conical. The pin may include a
shoulder or similar support to stabilize the transfer array (100).
The pin may be molded as part of a well plate. The pins may be on a
lattice without wells.
[0083] FIG. 13 is a cross-section diagram of an array element
showing a method of filling and mixing solutions using a transfer
array according to one example of the principles described herein.
The continuous lower sheet (1330) is formed similar to the lower
sheet but does not have a hole in the bottom the transfer element
(110). The upper sheet (120) includes a punch (1335) that when
depressed by a pusher plate (660), for example a pin opens a hole
in the continuous lower sheet (1330).
[0084] In this example, the continuous lower sheet (1330) may be
loaded with a fluid. The upper sheet (120) with the punch is then
applied over the continuous lower sheet (1330). This forms a
variety of sealed transfer elements (110). The lack of an opening
in the transfer element (110) reduces evaporation and the risk of
contamination. The transfer array is then placed over a well plate
(450) that may contain a second liquid in the wells of the well
plate (450). The upper sheet (120) is pressed down and the punch
(1335) creates a hole in the continuous lower sheet (1330). In one
example, the continuous lower sheet (1330) includes an access point
(140) similar to those described above for the upper sheet (120).
With a hole in the continuous lower sheet (1530), the two fluids
mix. The fluids can be agitated using the pressor plate (660). The
mixed fluids can be aspirated back into the transfer element (110)
and transferred to another well plate (450).
[0085] FIG. 14 is a cross-sectional diagram of a transfer element
(110) in a conformal well plate (450) according to one example of
the principles described herein. In this example, the well plate
(450) is shaped to conform to the lower sheet (130) of the transfer
array such that at least a portion of the lower sheet (130)
contacts the walls of the well. In one example, more than half the
lower sheet (130) in the well is in contact with a well wall.
[0086] In one example, a heating and/or cooling source (1440) is
available below the well plate (450). The wall of the transfer
element (110) is in contact with the well wall, heat transfer
between the heating or cooling element and the transfer volume in
enhanced. In contrast, an air gap between the lower sheet (130) and
the well wall serves as an insulator. In one example, at least half
the lower sheet (13) in the well is in contact with a wall of the
well.
[0087] In one example, the well plate (450) includes a pin or stop
that holds the lower sheet (130) of the transfer array (100)
slightly above the surface of the well plate (450). The gap between
the well plate (450) and the lower sheet (130) allows air flow to
aid in the aspiration and expulsion of fluid from the transfer
element (110). When the operations are done, the transfer array
(100) may be pressed down onto the well plate (450) to seal the
wells.
[0088] In one example, the stops are small pins that extend up from
the well plate (450), pass through holes in the lower sheet (130)
and contact a more flexible portion of the upper sheet (120). In
one example, the upper sheet (120) includes crosshair cuts that
align with the pins. The flaps of the crosshair cuts supporting the
transfer array (100) above the well plate (450) but the flaps
deflect under pressure, allowing the lower sheet (130) to seal the
wells of the well plate (450). In another example, the pins are
flexible and include a shoulder at a first height to support the
transfer array (100) above the well plate (450). To seal the wells,
the transfer array (100) is pressed down, causing the pins to
deflect. After the transfer array (100) has passed the shoulder,
the pins recoil and help hold the transfer array (100) in place. In
one example, the deflecting pins are reversible to allow the
transfer array (100) to be removed from the well plate (450). In
another example, the deflecting pins are not easily deflected when
the transfer array (100) is in the sealing position and the sealing
is effectively a one-way process. For example, the shoulder may
have a triangular shape where the slope of the triangle allows
locking but a flat or steep side of the triangle makes unlocking
difficult. In another example, the pins descend from the transfer
array (100), either as part of the upper sheet (120) and/or lower
sheet (130). The pins interact with holes or receiving features in
the well plate (450).
[0089] FIG. 15 shows an example a transfer array (100) with a
locking mechanism to help stabilize the upper sheet (120). The
locking mechanism may be associated with the pressor plate (660).
The locking mechanism includes a first support rail (1570). The
locking mechanism may also have additional support rails such as a
second support rail (1575).
[0090] In one example, the first support rail (1570) includes a
number of retaining features that pass through the upper sheet
(120) and lower sheet (130). The support rail (1570) is then moved
laterally to the surface of the transfer array (100). This cause
the retaining features to engage the transfer array. The retaining
features may serve to stabilize the position of the transfer array
(100). The retaining features may serve to hold the upper sheet
(120) and/or lower sheet (130) vertically stable or in contact with
each other. This is particularly useful when a pressor plate (660)
engages with the transfer elements (110) to expel or aspirate
fluid.
[0091] The system may also use a second support rail (1575). Like
the first support rail (1570) the second support rail (1575) also
passes through the upper sheet (120) and lower sheet (130) and
moves laterally relative to the transfer array (100). In one
example, the first and second support rails (1570, 1575) move in
opposite directions to create compression/tension in the upper
sheet (120) and/or lower sheet (130). This may enhance the
stability of the transfer array during operation. The first support
rail (1570) may also interact with the well plate (450). For
example, the well plate (450) and the transfer array (100) may
include coordinated openings through with the retention features of
the first and/or second support rails (1570, 1575) pass. The first
and/or second support rail (1570, 1575) may contact an upper
portion of the upper sheet (120) and press the transfer array (100)
against the well plate (450). The first and second support rails
(1570, 1575) may also include a plurality of parallel rails to form
a lattice or plate. In one example, the system uses a small number
of retaining features, e.g. 2 to 10. In another example, the system
has one retaining feature for each well. In a third example, the
system has two retaining features for each well, one moving in a
first direction and the other moving in a second direction.
[0092] The preceding description has been presented to illustrate
and describe examples of the principles described. This description
is not intended to be exhaustive or to limit these principles to
any precise form disclosed. Many modifications and variations are
possible in light of the above teaching.
[0093] Some additional examples consistent with this disclosure
include the following:
* * * * *